3K46

Crystal structure of full-length E. coli beta-glucuronidase

3K46 の概要

• エントリーDOI: 10.2210/pdb3k46/pdb
• 関連するPDBエントリー: 3K4A 3K4D
• 分子名称: Beta-glucuronidase (2 entities in total)
• 機能のキーワード: alpha/beta barrel, sugar-binding domain, beta-sandwich domain, glycosyl hydrolase, glycosidase, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 137493.91

構造登録者

Wallace, B.D.,Lane, K.T.,Redinbo, M.R. (登録日: 2009-10-05, 公開日: 2010-11-17, 最終更新日: 2023-09-06)

主引用文献

Wallace, B.D.,Wang, H.,Lane, K.T.,Scott, J.E.,Orans, J.,Koo, J.S.,Venkatesh, M.,Jobin, C.,Yeh, L.A.,Mani, S.,Redinbo, M.R.
Alleviating cancer drug toxicity by inhibiting a bacterial enzyme.
Science, 330:831-835, 2010

PubMed Abstract: The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.

PubMed: 21051639
DOI: 10.1126/science.1191175

実験手法

X-RAY DIFFRACTION (2.5 Å)